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Oral presentation

Innovative technology for studies on drug metabolism and related problems

Niels Krebsfaenger email, TU Meyer, S Janku and J Doehmer

GenPharmTox BioTech AG, 82152 Martinsried, Germany

author email† Presenting author

2002 Joint Annual Meeting of the Arbeitsgemeinschaft für Angewandte Humanpharmakologie (Association for Applied Human Pharmacology) and the American College of Clinical Pharmacology
Garmisch-Partenkirchen, Germany, 27-29 January 2002

AGAH 2002, 1:op006

Received: 25 March 2002
Published: 4 April 2002

Oral presentation

Cytochromes P450s are the key enzymes in the metabolism of most drugs and chemicals. All relevant human cytochromes P450s have been cloned and stably expressed individually in V79 Chinese hamster cells comprising the V79 Cell Battery™. V79 Chinese hamster cells were the host cells of choice because there is no background cytochrome P450 activity in these cells making the genetically engineered V79 cells a perfect and superior analytical tool for studying all metabolism related problems.

The V79 Cell Battery™ has already a proven record for generating high data quality with high predictive value in drug metabolism for humans long before clinical studies are being started. This is exemplified by the application the V79 cells expressing all relevant cytochrome P450 2D6 polymorphic forms or cytochromes P450 11B1 and 11B2 expressed in the adrenal gland and key enzymes in the steroid metabolism pathways.

V79h2D6 cell lines revealed unexpected relative enzymatic activities for the allele specific metabolism of some 2D6 substrates, e.g., variant 2D6*17 untypically showed comparable catalytic activity as the wild type 2D6*1.

V79h11B1 and 11B2 cells served as a tool to perform inhibition studies of azole derivatives with respect to the endogenous cortisol formation were identified: while fluconazole showed no inhibition, miconazole, ketoconazole, and clotrimazole showed nearly quantitative inhibition within the same concentration range.

The professional application of the V79 Cell Battery™ is supported by quality assurance including GLP certification. We want to serve and support your drug development process by yielding high quality data with high predictive value for humans.

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